Phenol-Soluble Modulin Toxins of Staphylococcus haemolyticus

TY - JOUR

T1 - Phenol-Soluble Modulin Toxins of Staphylococcus haemolyticus

AU - Da, Fei

AU - Joo, Hwang-Soo

AU - Cheung, Gordon Y C

AU - Villaruz, Amer E

AU - Rohde, Holger

AU - Luo, Xiaoxing

AU - Otto, Michael

PY - 2017

Y1 - 2017

N2 - Coagulase-negative staphylococci (CoNS) are important nosocomial pathogens and the leading cause of sepsis. The second most frequently implicated species, afterStaphylococcus epidermidis, isStaphylococcus haemolyticus. However, we have a significant lack of knowledge about what causes virulence ofS. haemolyticus, as virulence factors of this pathogen have remained virtually unexplored. In contrast to the aggressive pathogenStaphylococcus aureus, toxin production has traditionally not been associated with CoNS. Recent findings have suggested that phenol-soluble modulins (PSMs), amphipathic peptide toxins with broad cytolytic activity, are widespread in staphylococci, but there has been no systematic assessment of PSM production in CoNS other thanS. epidermidis. Here, we identified, purified, and characterized PSMs ofS. haemolyticus. We found three PSMs of the β-type, which correspond to peptides that before were described to have anti-gonococcal activity. We also detected an α-type PSM that has not previously been described. Furthermore, we confirmed thatS. haemolyticusdoes not produce a δ-toxin, as results from genome sequencing had indicated. All fourS. haemolyticusPSMs had strong pro-inflammatory activity, promoting neutrophil chemotaxis. Notably, we identified in particular the novel α-type PSM,S. haemolyticusPSMα, as a potent hemolysin and leukocidin. For the first time, our study describes toxins of this important staphylococcal pathogen with the potential to have a significant impact on virulence during blood infection and sepsis.

AB - Coagulase-negative staphylococci (CoNS) are important nosocomial pathogens and the leading cause of sepsis. The second most frequently implicated species, afterStaphylococcus epidermidis, isStaphylococcus haemolyticus. However, we have a significant lack of knowledge about what causes virulence ofS. haemolyticus, as virulence factors of this pathogen have remained virtually unexplored. In contrast to the aggressive pathogenStaphylococcus aureus, toxin production has traditionally not been associated with CoNS. Recent findings have suggested that phenol-soluble modulins (PSMs), amphipathic peptide toxins with broad cytolytic activity, are widespread in staphylococci, but there has been no systematic assessment of PSM production in CoNS other thanS. epidermidis. Here, we identified, purified, and characterized PSMs ofS. haemolyticus. We found three PSMs of the β-type, which correspond to peptides that before were described to have anti-gonococcal activity. We also detected an α-type PSM that has not previously been described. Furthermore, we confirmed thatS. haemolyticusdoes not produce a δ-toxin, as results from genome sequencing had indicated. All fourS. haemolyticusPSMs had strong pro-inflammatory activity, promoting neutrophil chemotaxis. Notably, we identified in particular the novel α-type PSM,S. haemolyticusPSMα, as a potent hemolysin and leukocidin. For the first time, our study describes toxins of this important staphylococcal pathogen with the potential to have a significant impact on virulence during blood infection and sepsis.

KW - Amino Acid Sequence

KW - Bacterial Proteins

KW - Bacterial Toxins

KW - Hemolysin Proteins

KW - Hemolysis

KW - Humans

KW - Leukocidins

KW - Neutrophils

KW - Sepsis

KW - Staphylococcal Infections

KW - Staphylococcus

KW - Staphylococcus aureus

KW - Staphylococcus epidermidis

KW - Staphylococcus haemolyticus

KW - Virulence

KW - Virulence Factors

KW - Journal Article

U2 - 10.3389/fcimb.2017.00206

DO - 10.3389/fcimb.2017.00206

M3 - SCORING: Journal article

C2 - 28596942

VL - 7

SP - 206

JO - FRONT CELL INFECT MI

JF - FRONT CELL INFECT MI

SN - 2235-2988

ER -